This application seeks to continue for years 06-10 the postdoctoral training grant entitled, Research Training Program for Medical Geneticists. The program's overall goal is to provide a mentored research experience for M.D. medical geneticists to perform productive independent basic/ translational research and to develop the skills and experience required to effectively compete for federal funding and become academic leaders in medical genetics and genomics. The program's emphasis is on basic and translational research in genetics and genomics, including the application of recent and continuing advances in genome sequencing and analysis, bioinformatics, and systems biology analyses, towards the understanding of the genetics/genomics of monogenic and complex traits, and to translate these findings into improved diagnosis, prevention, and new effective therapies. MD trainees chosen for this program will have completed a residency in Medical Genetics. Our Medical Genetics residency programs provides a pipeline of outstanding candidates who have demonstrated a commitment to a basic/ translational research career. Highly qualified medical geneticist applicants from other residency training programs and underrepresented minority candidates will also be recruited. Trainees will be supported for a period of 2 to 3 years under close supervision of one of our Research Mentor faculty, and each trainee will have an appropriate Advisory Committee. Previous trainees from this program have successfully obtained academic/ industry positions and have applied for/ received federal funding. This training program builds upon considerable resources at Mount Sinai including: 1) an exceptional group of funded Research Mentors in multidisciplinary research programs, as well as faculty who serve as Clinical Laboratory Preceptors and Research Core Directors; 2) our accredited Medical Genetics training programs in all the ABMG specialties; 3) didactic elective courses in basic translational research methodology, and responsible conduct of research, 4) an infrastructure of Shared Research Facilities (SRFs) and disease-oriented and core-technology-based research institutes, including our new Institute for Genomics and Multiscale Biology. All trainees will participate in a monthly Training Grant Conference, our weekly work-in progress conference, weekly Genetics/Genomics seminar series, and our annual Research Day with our External Advisory Committee. This training program will meet a critical need for independent medical geneticists who can translate advances in genetics/ genomics into improved diagnosis and treatment of human disease. !